Functional evidence for derivation of systemic histiocytic neoplasms from
hematopoietic stem/progenitor cells
#MMPMID28566492
Durham BH
; Roos-Weil D
; Baillou C
; Cohen-Aubart F
; Yoshimi A
; Miyara M
; Papo M
; Hélias-Rodzewicz Z
; Terrones N
; Ozkaya N
; Dogan A
; Rampal R
; Urbain F
; Le Fèvre L
; Diamond EL
; Park CY
; Papo T
; Charlotte F
; Gorochov G
; Taly V
; Bernard OA
; Amoura Z
; Abdel-Wahab O
; Lemoine FM
; Haroche J
; Emile JF
Blood
2017[Jul]; 130
(2
): 176-180
PMID28566492
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Langerhans cell histiocytosis (LCH) and the non-LCH neoplasm Erdheim-Chester
disease (ECD) are heterogeneous neoplastic disorders marked by infiltration of
pathologic macrophage-, dendritic cell-, or monocyte-derived cells in tissues
driven by recurrent mutations activating MAPK signaling. Although recent data
indicate that at least a proportion of LCH and ECD patients have detectable
activating kinase mutations in circulating hematopoietic cells and bone
marrow-based hematopoietic progenitors, functional evidence of the cell of origin
of histiocytosis from actual patient materials has long been elusive. Here, we
provide evidence for mutations in MAPK signaling intermediates in CD34(+) cells
from patients with ECD and LCH/ECD, including detection of shared origin of LCH
and acute myelomonocytic leukemia driven by TET2-mutant CD34(+) cell progenitors
in one patient. We also demonstrate functional self-renewal capacity for CD34(+)
cells to drive the development of histiocytosis in xenotransplantation assays in
vivo. These data indicate that the cell of origin of at least a proportion of
patients with systemic histiocytoses resides in hematopoietic progenitor cells
prior to committed monocyte/macrophage or dendritic cell differentiation and
provide the first example of a patient-derived xenotransplantation model for a
human histiocytic neoplasm.
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